Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus

Fangzhu Zhao, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Zachary T. Berndsen, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Nuria Pedreño-Lopez, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Alison Burns, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Joel D. Allen, School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.
Shawn Barman, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Wen-Hsin Lee, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Srirupa Chakraborty, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
Sandrasegaram Gnanakaran, Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
Leigh M. Sewall, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Gabriel Ozorowski, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Oliver Limbo, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Ge Song, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Peter Yong, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Sean Callaghan, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Jessica Coppola, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Kim L. Weisgrau, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Jeffrey D. Lifson, AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, 21701, USA.
Rebecca Nedellec, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Thomas B. Voigt, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Fernanda Laurino, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Johan Louw, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Brandon C. Rosen, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Michael Ricciardi, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Max Crispin, School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.
Ronald C. Desrosiers, Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
Eva G. Rakasz, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, 53715, USA.
David I. Watkins, Department of Pathology, George Washington University, Washington, DC, 20037, USA.
Raiees Andrabi, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA. andrabi@scripps.edu.
Andrew B. Ward, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA. andrew@scripps.edu.
Dennis R. Burton, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA. burton@scripps.edu.
Devin Sok, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA. dsok@iavi.org.

Document Type

Journal Article

Publication Date

9-6-2022

Journal

Nature communications

Volume

13

Issue

1

DOI

10.1038/s41467-022-32783-2

Abstract

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.

Department

Pathology

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